Cancer of the prostate is the most commonly diagnosed cancer in men and is the second most common cause of cancer death (Carter and Coffey, Prostate 16:39-48, 1990; Armbruster et al., Clinical Chemistry 39:181, 1993). If detected at an early stage, prostate cancer is potentially curable. However, a majority of cases are diagnosed at later stages when metastasis of the primary tumor has already occurred (Wang et al., Meth. Cancer Res. 19:179, 1982). Even early diagnosis is problematic because not all individuals who test positive in these screens develop cancer.
Present treatment for prostate cancer includes radical prostatectomy, radiation therapy, or hormonal therapy. With surgical intervention, complete eradication of the tumor is not always achieved and the observed re-occurrence of the cancer (12-68%) is dependent upon the initial clinical tumor stage (Zietman et al., Cancer 71:959, 1993). Thus, alternative methods of treatment including prophylaxis or prevention are desirable.
Breast cancer is the most common type of epithelial cancer among women in the United States. More than 180,000 women are diagnosed with breast cancer each year. About one in eight women in the United States (approximately 12.8 percent) will develop breast cancer during her lifetime. At present there are no curative therapies available for breast cancer that has metastasized from its site of origination.
Up to 30% of 180,000 United States patients with potentially curable early-stage breast and prostate cancer will fail standard surgical or radiotherapy in 2004. In addition, patients with metastatic prostate cancer and the majority of patients with metastatic breast cancer enjoy limited benefit of standard chemotherapy and hormone-based therapies. Immunotherapy may have great potential to improve on these results, combining the tumor specificity of cell-mediated immunity with freedom from toxic chemotherapies.
Immunotherapy involves evoking an immune response against cancer cells based on their production of target antigens. Immunotherapy based on cell-mediated immune responses involves generating a cell-mediated response to cells that produce particular antigenic determinants, while immunotherapy based on humoral immune responses involves generating specific antibodies to cells that produce particular antigenic determinants.
Recent studies show that immunotherapy of cancer patients may be dramatically improved by the finding that CD8+ CTL recognize and kill tumor cells that display peptides from tumor-associated antigens within MHC Class I molecules. In clinical studies it has been found that effector CD8+ T cells play a major role in tumor regression. Several tumor antigens in prostate cancer models have been identified and HLA allele-specific peptides from those prostate cancer-associated antigens have been identified as CD8+ T cell epitopes. For example, HLA-A2.1 binding peptides were described that were derived from prostate specific antigen (PSA) (Correale et al., J Immunol 161:3186, 1998), prostate-specific membrane antigen (PSMA) (Tjoa et al., Prostate 28:65, 1996), prostate stem cell antigen (PSCA) (Kiessling et al., Int J Cancer 102:390, 2002), and prostate acid phosphatase (Peshwa et al., Prostate 36:129, 1998). For PSA, clinical trials are in progress using different vaccine strategies. However, there clearly is a need to identify additional antigens to aid in the diagnosis of prostate cancer, and for use as additional therapeutic agents.